The over-arching objective of this program of investigation is to identify the pathogenesis and ontogeny of Specific Language Impairment (SLI). The specific aims for this cycle of funding are: 1)Document longitudinal language acquisition of twins ages 2-14 years, and compare to singletons at 2, 6, 9, and 14 years; 2) Identify twinning effects on early language acquisition and describe the longitudinal course of such effects; 3) Develop multivariate models of biological and environmental risk for twinning effects and for SLI, and compare for possible overlapping etiology; and 4) Evaluate models of age-graded genetic effects via converging methods. The following three hypotheses are evaluated: First, developmental changes in language ability are mediated through changes in gene expression over time, and these changes are mediated in part by changes in methylation patterns, in light of recent evidence of methylation alternations in higher cognitive disorders. Second, abnormalities in gene expression underlie some types of language impairment via abnormal methylation patterns in regulatory sites. Third, twinning effects reflect early complex interactions of genetic, perinatal, and environmental effects that can clarify some of the influences establishing risk for language onset, risks that may modulate over time leaving the robust ongoing risks for persistent SLI. The study extends a current lagged cohort longitudinal study of 1460 twin children, their family members, and 237 control children, with a fifth time of measurement at 14 years, to add to the obtained longitudinal assessments at 2, 4, 6, and 9 years. The protocol includes extensive family and environmental data as well as a detailed protocol of language, speech, and cognitive skills including reading. In addition, at 14 years the measurements will capture social and academic variability across children as they prepare for their transition to adult life. In this cycle of funding data collection will be completed for family DNA and behavioral assessments following the same protocol for the full sample of twin and singleton probands. The study design incorporates unique opportunities to evaluate twinning effects by comparison to large population-based samples of singletons on a wide variety of social, cognitive, and academic assessments. At the molecular genetics level, family-based target gene investigations will be conducted along with the first investigations of methylation regulation in discordant MZ co-twins. The findings will document language growth, and identify genetic, epigenetic, and environmental drivers of that growth. Potential clinical translations of the outcomes include better diagnostic methods, to identify SLI in twins as well as singletons, to identify children at long term risk for SLI, reading impairments, and limited adaptive outcomes in adolescence; and to identify growth-defined intervention targets for specific dimensions of language acquisition. PUBLIC HEALTH RELEVANCE: Specific Language Impairment (SLI) is an inherited condition although the specific genetic influences are not identified. Twin children provide unique opportunities to study genetic and environmental influences on language acquisition, and to differentiate late language emergence from SLI. This study documents language acquisition in a large sample of twins from 2 to 14 years, with analyses to evaluate environmental and genetic effects including investigation of targeted genes.